Systemic lupus erythematosus (SLE) patients without major overt neurological or psychiatric (NP) disorders have demonstrated cognitive dysfunction suggesting relatively subtle but clinically significant CNS involvement. Difficult diagnostic and treatment decisions are frequently necessary in these patients with cognitive abnormalities, and a better understanding of their underlying pathogenesis is critical to a rational approach to their management. We propose to identify potential mechanisms of cognitive dysfunction in SLE patients by examining quantitative brain structures (via MRI; magnetic resonance imaging), and neuronal metabolites (via MRS; proton magnetic resonance spectroscopy) in cognitively impaired SLE patients without NP disorders (CI-SLE). The specific aims of this proposal are first to compare CI-SLE to non-cognitively impaired SLE (NCI-SLE) and healthy control subjects on select quantitative MRI brain structures (whole brain and hippocampus) and proton MRS neurometabolites (NAA/Cr hippocampal structures and NAA/Cr; NAA/Cr and Cho/Cr in normal appearing white matter in frontal and parieto-occipital regions). Secondly, we aim to examine the relationship between cognitive deficits, brain structures and neurometabolites in the SLE patients. We will begin the analyses with a global relationship between a cognitive impairment index and whole brain measurement. We will then evaluate learning and memory measures in relation to the size of the hippocampus and NAA/Cr levels in that area. We will next examine attention/information processing in relation to total volume of white matter hyperintensities. Then we will examine NAA/Cr and Ch/Cr levels in frontal area of the brain in relation to attention/information processing and executive skills. Finally we will explore whether subjective cognitive complaints of SLE patients are associated with specific objective cognitive deficits, quantitative brain structures and select neurometabolites. We believe that understanding the biological abnormalities associated with cognitive dysfunction in SLE patients will guide further investigations directed at the underlying mechanisms of CNS changes in SLE. This will better prepare clinicians with clear diagnostic avenues and better treatment options in the future. [unreadable] [unreadable]